miR-935 Promotes Liver Cancer Cell Proliferation and Migration by Targeting SOX7

Oncol Res. 2017 Mar 13;25(3):427-435. doi: 10.3727/096504016X14747300207374. Epub 2016 Sep 30.

Abstract

Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. Aberrant expression of microRNA-935 (miR-935) has been reported in cancer studies. However, its expression and mechanism in HCC remain unclear. In our study, we found that miR-935 was upregulated in liver cancer tissues and cells. Overexpression of miR-935 in liver cells promoted cell proliferation, tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced cell proliferation, tumorigenicity, and cell cycle progression. These changes in the properties of HCC cells were associated with upregulation of two well-known cellular G1/S transitional regulators: cyclin D1 and c-Myc. Additionally, we identified SOX7 as a direct target of miR-935. Overexpression of miR-935 inhibited SOX7 expression but promoted the levels of c-Myc and cyclin D1, which promotes cell proliferation and tumorigenesis; knockdown of miR-935 increased SOX7 level and inhibited c-Myc and cyclin D1 expression, whereas SOX7 silencing could promote cell proliferation, cell motility, and invasiveness in vitro. Our findings suggest that miR-935 represents a biomarker and a potential new target in HCC progression by suppressing SOX7 expression.

MeSH terms

  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics
  • G1 Phase / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-myc / genetics
  • S Phase / genetics
  • SOXF Transcription Factors / genetics*
  • Up-Regulation / genetics

Substances

  • MIRN-935 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • SOX7 protein, human
  • SOXF Transcription Factors
  • Cyclin D1